Magnetothermal Control of Temperature-Sensitive Repressors in Superparamagnetic Iron Nanoparticle-Coated Bacillus subtilis
Magnetothermal Control of Temperature-Sensitive Repressors in Superparamagnetic Iron Nanoparticle-Coated Bacillus subtilis
复制标题
超顺磁性铁纳米颗粒包被的枯草芽孢杆菌中温度敏感抑制子的磁热控制
DOI：
10.1021/acsnano.2c06239
复制
发表时间：
2022
期刊：
影响因子：
17.1
通讯作者：
Contag, Christopher H.
中科院分区：
文献类型：
--
作者：
Greeson, Emily M.;Madsen, Cody S.;Makela, Ashley V.;Contag, Christopher H.
超顺磁性氧化铁纳米粒子（SPION）在磁共振成像（MRI）和磁性粒子成像（MPI）中用作造影剂，所得图像可用于引导磁热加热。交变磁场 (AMF) 会导致 SPION 区域的局部温度升高，我们研究了磁热疗调节细菌转录温度敏感抑制子 (TSR) 的能力。 TSR TlpA39 源自革兰氏阴性细菌，用于革兰氏阳性枯草芽孢杆菌中报告基因表达的热控制。 B.体外加热枯草芽孢杆菌与控制细菌荧光素酶表达的 TlpA39 一起导致报告基因转录物增加 14.6 倍（12 小时；h）和 1.8 倍（1 小时），生物发光增加 10.0 倍（12 小时）和 12.1 倍（1 小时）。发展磁热控制，B.枯草芽孢杆菌细胞被三种 SPION 变体包被。电子显微镜结合能量色散 X 射线光谱揭示了 B 上 SPION 的外部关联和保留。枯草芽孢杆菌。此外，使用长持续时间的 AMF，我们证明了 SPION-coatedB 中 TSR 的磁热感应。枯草芽孢杆菌的生物发光最多增加 5.6 倍。肌肉注射 SPION 包被的 B 后。枯草芽孢杆菌中，组织学显示 SPION 保留在与细菌相同的位置。对于体内研究，由于麻醉限制，1 小时的 AMF 是最大暴露量。无论是体外还是体内，AMF处理1小时后生物发光均无变化。将 TSR 与磁热能配对，使用 SPION 与 AMF 进行局部加热，可以实现转录控制，从而扩大靶向细菌疗法的选择。
Superparamagnetic iron oxide nanoparticles (SPIONs) are used as contrast agents in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), and resulting images can be used to guide magnetothermal heating. Alternating magnetic fields (AMF) cause local temperature increases in regions with SPIONs, and we investigated the ability of magnetic hyperthermia to regulate temperature-sensitive repressors (TSRs) of bacterial transcription. The TSR, TlpA39, was derived from a Gram-negative bacterium and used here for thermal control of reporter gene expression in Gram-positive,Bacillus subtilis. In vitroheating ofB. subtiliswith TlpA39 controlling bacterial luciferase expression resulted in a 14.6-fold (12 hours; h) and 1.8-fold (1 h) increase in reporter transcripts with a 10.0-fold (12 h) and 12.1-fold (1 h) increase in bioluminescence. To develop magnetothermal control,B. subtiliscells were coated with three SPION variations. Electron microscopy coupled with energy dispersive X-ray spectroscopy revealed an external association with, and retention of, SPIONs onB. subtilis. Furthermore, using long duration AMF we demonstrated magnetothermal induction of the TSRs in SPION-coatedB. subtiliswith a maximum of 5.6-fold increases in bioluminescence. After intramuscular injections of SPION-coatedB. subtilis, histology revealed that SPIONs remained in the same locations as the bacteria. Forin vivostudies, 1 h of AMF is the maximum exposure due to anesthesia constraints. Bothin vitroandin vivo, there was no change in bioluminescence after 1 h of AMF treatment. Pairing TSRs with magnetothermal energy using SPIONs for localized heating with AMF can lead to transcriptional control that expands options for targeted bacteriotherapies.